Method for manufacturing drometrizole trisiloxane (DMTS)

Abstract

To provide a method for manufacturing DMTS.SOLUTION: The present invention relates to a method for preparing DMTS, which does not use a solvent having a high boiling point, uses phosphate, does not use any reaction auxiliaries, has a very short reaction time, and causes low impurities, thereby ensuring high purity and yield.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for preparing drometrizole trisiloxane (DMTS), and more specifically to a method for preparing DMTS with high purity and yield by using no high-boiling point solvent, no phosphate salts, no reaction aids, a very short reaction time, and few impurities. [Background technology]

[0002] Sunscreens used to prevent skin damage caused by ultraviolet rays can be broadly divided into chemical sunscreens and physical sunscreens. Well-known chemical sunscreens, which work by chemically absorbing ultraviolet rays, include organic blockers such as cinnamates, salicylates, and benzophenones, while well-known physical sunscreens, which work by physically scattering and blocking ultraviolet rays, include inorganic blockers such as titanium dioxide and zinc oxide.

[0003] Chemical sunscreens have the advantage of providing excellent UV blocking effects, but they have the disadvantage of being applicable only in a narrow wavelength range, causing stickiness and greasiness when used in cosmetic compositions, making them uncomfortable to use, and there is a risk that they may be absorbed into the skin in their molecular form, causing skin irritation.

[0004] Physical sunscreens tend to cause less skin irritation than chemical sunscreens, but they have the drawback of leaving a heavy feeling and a white cast.

[0005] Meanwhile, drometrizole trisiloxane (DMTS), known by the trade names Mexoryl XL or Silatrizole, is widely used as a sunscreen.

[0006] Regarding the preparation of DMTS, various studies have been conducted to effectively remove water and impurities to produce a highly pure compound.

[0007] However, conventional techniques require long reaction times, complicated reaction processes, and high impurity contents in the compounds, making them unsuitable for stable use as raw materials for cosmetics, pharmaceuticals, electronic devices, and the like. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] Korean Patent Registration No. 10-2635085 [Patent Document 2] Korean Patent No. 10-2261129 [Patent Document 3] Korean Patent Registration No. 10-0636953 Summary of the Invention [Problem to be solved by the invention]

[0009] The present invention is intended to solve the problems of the prior art and aims to provide a method for preparing DMTS with high purity and high yield, without using a high-boiling point solvent, a phosphate salt, or any reaction aids, and with a very short reaction time and few impurities. [Means for solving the problem]

[0010] To achieve the above object, the present invention provides a method for preparing a first mixture by mixing drometrizole, a phosphate salt, and a solvent; (b) adding methallyl halide to the first mixture and reacting to prepare a first product; (c) adding distilled water to the first product, followed by phase separation to prepare a second mixture; (d) distilling the second mixture to remove the solvent and then heating to prepare methallyl drometrizole; (e) mixing the methallyl drometrizole with a solvent to form a third mixture; (f) cooling, crystallizing, filtering, and drying the third mixture to obtain methallyl drometrizole; (g) mixing the methallyl drometrizole with a solvent to form a fourth mixture; (h) combining the fourth mixture with a catalyst solution to form a fifth mixture; (i) mixing and reacting the fifth mixture with a heptamethyltrisiloxane (HMTS) solution to prepare a second product; (j) distilling the second product to remove solvent and then adding a solvent to form a sixth mixture; (k) cooling, crystallizing, filtering, and drying the sixth mixture to obtain drometrizole trisiloxane (DMTS).

[0011] In one embodiment of the present invention, the phosphate in step (a) is tripotassium phosphate.

[0012] In one embodiment of the present invention, the step (a) is characterized by using a mixture of ethyl acetate and dimethyl sulfoxide as the solvent.

[0013] In one embodiment of the present invention, step (d) is characterized in that the second mixture is distilled to remove the solvent, and then reacted at 190 to 250°C for 30 minutes to 5 hours to prepare methallyl drometrizole.

[0014] In one embodiment of the present invention, the step (e) is characterized by using a mixture of ethyl acetate and methanol as the solvent.

[0015] In one embodiment of the present invention, the step (g) is characterized by using methyl ethyl ketone or acetone as the solvent. [Effects of the Invention]

[0016] The present invention provides a method for preparing DMTS with high purity and high yield, without using a high-boiling point solvent, using a phosphate salt, or any reaction aids, with a very short reaction time and few impurities. DETAILED DESCRIPTION OF THE INVENTION

[0017] The present invention will be described in detail below with reference to examples. The terms, examples, etc. used in the present invention are merely illustrative examples to explain the present invention in more detail and to aid the understanding of those skilled in the art, and should not be construed as limiting the scope of the present invention.

[0018] Unless otherwise defined, all technical and scientific terms used herein have the meaning commonly understood by one of ordinary skill in the art to which this invention belongs.

[0019] The present invention includes the steps of: (a) preparing a first mixture by combining drometrizole, a phosphate salt, and a solvent; (b) adding methallyl halide to the first mixture and reacting to prepare a first product; (c) adding distilled water to the first product, followed by phase separation to prepare a second mixture; (d) distilling the second mixture to remove the solvent and then heating to prepare methallyl drometrizole; (e) mixing the methallyl drometrizole with a solvent to form a third mixture; (f) cooling, crystallizing, filtering, and drying the third mixture to obtain methallyl drometrizole; (g) mixing the methallyl drometrizole with a solvent to form a fourth mixture; (h) combining the fourth mixture with a catalyst solution to form a fifth mixture; (i) mixing and reacting the fifth mixture with a heptamethyltrisiloxane (HMTS) solution to prepare a second product; (j) distilling the second product to remove solvent and then adding a solvent to form a sixth mixture; (k) cooling, crystallizing, filtering, and drying the sixth mixture to obtain drometrizole trisiloxane (DMTS).

[0020] The present invention does not use a high-boiling point solvent, uses a phosphate, does not use any reaction aids, and has a short reaction time and few impurities, making it possible to prepare DMTS with high purity and yield.

[0021] [ka] Methallyl Drometrizole

[0022] In the step (a), the first mixture may be prepared by mixing drometrizole, a phosphate salt, and a solvent at 50 to 100° C. under a nitrogen atmosphere.

[0023] The first mixture may contain 50 to 90 parts by weight of drometrizole and 60 to 90 parts by weight of phosphate relative to 100 parts by weight of solvent. When the contents are within the above ranges, the yield and purity can be maximized.

[0024] The phosphate may be monopotassium phosphate, dipotassium phosphate, tripotassium phosphate, monosodium phosphate, disodium phosphate, trisodium phosphate, lithium phosphate, monocalcium phosphate, dicalcium phosphate, tricalcium phosphate, monomagnesium phosphate, dimagnesium phosphate, or trimagnesium phosphate, and it is preferable to use tripotassium phosphate.

[0025] In the present invention, it is preferable to use 1 to 1.5 equivalents of phosphate per equivalent of drometrizole, and when the content satisfies the above numerical range, the yield and purity can be maximized.

[0026] The solvent may be benzyl alcohol, ethanol, methanol, acetone, dimethyl sulfoxide, ethyl acetate, or the like.

[0027] In the present invention, a mixture of ethyl acetate and dimethyl sulfoxide may be used as the solvent, and in this case, the weight ratio of ethyl acetate to dimethyl sulfoxide is preferably 70 to 90:10 to 30. When the weight ratio satisfies the above numerical range, the yield and purity can be maximized.

[0028] The step (b) may include adding methallyl halide to the first mixture and reacting to prepare a first product.

[0029] At this time, the methallyl halide may be added dropwise for 10 to 100 minutes, and then reacted at 50 to 100° C. for 1 to 10 hours to prepare the first product.

[0030] As the methallyl halide, methallyl iodide, methallyl chloride, methallyl bromide, etc. may be used, and it is preferable to use methallyl chloride.

[0031] The content of the methallyl halide is preferably 20 to 60 parts by weight relative to 100 parts by weight of the solvent.

[0032] In the present invention, it is preferable to use 1 to 1.5 equivalents of methallyl halide per equivalent of drometrizole, and when the content satisfies the above numerical range, the yield and purity can be maximized.

[0033] In the step (c), distilled water may be added to the first product, followed by phase separation at 30 to 100°C to prepare the second mixture.

[0034] The content of the distilled water is preferably 100 to 600 parts by weight relative to 100 parts by weight of the solvent.

[0035] At this time, in the present invention, 100 to 300 parts by weight of distilled water may be added to the first product, followed by primary phase separation, and then 100 to 300 parts by weight of distilled water may be added, followed by secondary phase separation.

[0036] In the step (d), the second mixture may be distilled under atmospheric pressure to remove the solvent, and then reacted at 190 to 250° C. for 30 minutes to 5 hours to prepare methallyl drometrizole.

[0037] In the step (e), the third mixture may be prepared by mixing the methallyl drometrizole with a solvent at 60 to 100°C.

[0038] The solvent may be isopropyl alcohol, benzyl alcohol, ethanol, methanol, acetone, ethyl acetate, or the like.

[0039] In the present invention, a mixture of ethyl acetate and methanol may be used as the solvent, and in this case, the weight ratio of ethyl acetate to methanol is preferably 20 to 50:50 to 80. When the weight ratio satisfies the above numerical range, the yield and purity can be maximized.

[0040] In the present invention, it is preferable to use 100 to 300 parts by weight of a solvent with respect to 100 parts by weight of methallyl drometrizole.

[0041] Step (f) may include cooling, crystallizing, filtering, and drying the third mixture to obtain methallyl drometrizole.

[0042] The third mixture may form crystals at 50 to 60° C. upon cooling, be cooled to room temperature and stirred, and then be cooled again to 0 to 5° C. and stirred for 1 to 5 hours.

[0043] The crystallized third mixture may be filtered to separate it into a filtrate and a solid, and then the solid may be dried to obtain methallyldrometrizole.

[0044] In the step (g), the fourth mixture may be prepared by mixing the methallyl drometrizole and a solvent at 20 to 60° C. under a nitrogen atmosphere.

[0045] The fourth mixture may contain 100 to 300 parts by weight of methallyl drometrizole per 100 parts by weight of the solvent. When the content satisfies the above range, the yield and purity can be maximized.

[0046] The solvent may be methyl ethyl ketone, isopropyl alcohol, acetone, toluene, ethyl acetate, or the like.

[0047] In the present invention, it is preferable to use methyl ethyl ketone or acetone as the solvent.

[0048] Furthermore, in the present invention, a mixture of methyl ethyl ketone and acetone may be used as the solvent, and in this case, the weight ratio of methyl ethyl ketone to acetone is preferably 70-90:10-30. When the weight ratio satisfies the above numerical range, the yield and purity can be maximized.

[0049] In the step (h), the fourth mixture and a catalyst solution may be mixed at 60 to 120°C to prepare a fifth mixture.

[0050] The catalyst solution contains a catalyst and a solvent, and the catalyst may be a Karstedt catalyst, platinum, or the like.

[0051] The solvent may be methyl ethyl ketone, isopropyl alcohol, acetone, toluene, ethyl acetate, or the like.

[0052] In the present invention, it is preferable to use methyl ethyl ketone or acetone as the solvent.

[0053] Furthermore, in the present invention, a mixture of methyl ethyl ketone and acetone may be used as the solvent, and in this case, the weight ratio of methyl ethyl ketone to acetone is preferably 70-90:10-30. When the weight ratio satisfies the above numerical range, the yield and purity can be maximized.

[0054] The catalyst solution preferably contains 0.1 to 5 parts by weight of catalyst per 100 parts by weight of solvent.

[0055] In the present invention, it is preferable to use 5 to 30 parts by weight of the catalyst solution with respect to 100 parts by weight of the fourth mixture.

[0056] Step (i) may include mixing and reacting the fifth mixture with a heptamethyltrisiloxane (HMTS) solution to prepare a second product.

[0057] At this time, the heptamethyltrisiloxane solution may be added dropwise over 10 to 30 minutes, followed by reaction at 60 to 120°C for 1 to 10 hours to prepare the second product.

[0058] The heptamethyltrisiloxane solution may include heptamethyltrisiloxane and a solvent.

[0059] The solvent may be methyl ethyl ketone, isopropyl alcohol, acetone, toluene, ethyl acetate, or the like.

[0060] In the present invention, it is preferable to use methyl ethyl ketone or acetone as the solvent.

[0061] Furthermore, in the present invention, a mixture of methyl ethyl ketone and acetone may be used as the solvent, and in this case, the weight ratio of methyl ethyl ketone to acetone is preferably 70-90:10-30. When the weight ratio satisfies the above numerical range, the yield and purity can be maximized.

[0062] The heptamethyltrisiloxane solution preferably contains 300 to 1,000 parts by weight of heptamethyltrisiloxane per 100 parts by weight of the solvent.

[0063] In the present invention, it is preferable to use 30 to 70 parts by weight of the heptamethyltrisiloxane solution per 100 parts by weight of the fifth mixture.

[0064] Furthermore, in the present invention, it is preferable to use 1 to 1.5 equivalents of heptamethyltrisiloxane per equivalent of methallyldrometrizole, and when the content satisfies the above numerical range, the yield and purity can be maximized.

[0065] In the step (j), the second product may be distilled to remove the solvent, and then a solvent may be added and mixed at 30 to 80°C to prepare a sixth mixture.

[0066] The entrainer may be isopropyl alcohol, benzyl alcohol, ethanol, methanol, acetone, ethyl acetate, or the like.

[0067] In the present invention, a mixture of acetone and methanol may be used as the solvent, and in this case, the weight ratio of acetone to methanol is preferably 20 to 50:50 to 80. When the weight ratio satisfies the above numerical range, the yield and purity can be maximized.

[0068] In the present invention, it is preferable to use 200 to 600 parts by weight of a solvent with respect to 100 parts by weight of methallyl drometrizole.

[0069] Step (k) may include cooling, crystallizing, filtering, and drying the sixth mixture to obtain drometrizole trisiloxane (DMTS).

[0070] The sixth mixture may form crystals at 25 to 30° C. upon cooling, and may then be cooled to room temperature and stirred, and then cooled again to 0 to 5° C. and stirred for 1 to 5 hours.

[0071] The crystallized sixth mixture may be filtered to separate the filtrate and the solids, and the solids may then be dried to obtain drometrizole trisiloxane.

[0072] The present invention does not use a high-boiling point solvent, only uses phosphate, does not use any reaction aids, and has a very short reaction time and few impurities, making it possible to prepare DMTS with high purity and yield.

[0073] The present invention will be described in detail below with reference to examples and comparative examples. The following examples are merely illustrative for carrying out the present invention, and the content of the present invention is not limited to the following examples. [Example]

[0074] A first mixture was prepared by mixing 60 parts by weight of drometrizole, 70 parts by weight of tripotassium phosphate, 85 parts by weight of ethyl acetate, and 15 parts by weight of dimethyl sulfoxide at 65° C. under a nitrogen atmosphere.

[0075] To the first mixture, 40 parts by weight of methallyl chloride was added dropwise over 30 minutes, and then the mixture was reacted at 80° C. for 5 hours to prepare a first product.

[0076] A second mixture was prepared by adding 250 parts by weight of distilled water to the first product, followed by phase separation at 50°C.

[0077] The second mixture was distilled under atmospheric pressure to remove the solvent, and then reacted at 200° C. for 2 hours to prepare methallyl drometrizole.

[0078] A third mixture was prepared by mixing 100 parts by weight of the methallyl drometrizole, 70 parts by weight of ethyl acetate, and 130 parts by weight of methanol at 70°C.

[0079] The third mixture was cooled to room temperature and stirred, then cooled again to 5°C, and stirred for 2 hours to crystallize, filtered, and dried to obtain methallyl drometrizole (pale yellow crystal; yield 94.5%).

[0080] A fourth mixture was prepared by mixing 150 parts by weight of the methallyl drometrizole and 100 parts by weight of methyl ethyl ketone under a nitrogen atmosphere at room temperature.

[0081] A fifth mixture was prepared by mixing 100 parts by weight of the fourth mixture with 15 parts by weight of a catalyst solution at 75° C. The catalyst solution contained 1 part by weight of Karstedt's catalyst (a xylene solution containing 2% platinum) and 100 parts by weight of methyl ethyl ketone.

[0082] A second product was prepared by adding 50 parts by weight of a heptamethyltrisiloxane (HMTS) solution dropwise to 100 parts by weight of the fifth mixture over 30 minutes, followed by a reaction at 75° C. for 5 hours, whereby the heptamethyltrisiloxane solution contained 500 parts by weight of heptamethyltrisiloxane and 100 parts by weight of methyl ethyl ketone.

[0083] The second product was distilled to remove the solvent, and then acetone and methanol were added and mixed at 50° C. to prepare a sixth mixture, in which 105 parts by weight of acetone and 195 parts by weight of methanol were used per 100 parts by weight of methallyl drometrizole.

[0084] The sixth mixture was cooled to room temperature and stirred, then cooled again to 5°C and stirred for 2 hours to allow crystallization, which was then filtered and dried to obtain drometrizole trisiloxane (white crystal; yield 91.4%). [Example]

[0085] Drometrizole trisiloxane was obtained in the same manner as in Example 1, except that 65 parts by weight of ethyl acetate and 35 parts by weight of dimethyl sulfoxide were used. [Example]

[0086] Drometrizole trisiloxane was obtained in the same manner as in Example 1, except that 95 parts by weight of ethyl acetate and 5 parts by weight of dimethyl sulfoxide were used. [Example]

[0087] Drometrizole trisiloxane was obtained in the same manner as in Example 1, except that 50 parts by weight of tripotassium phosphate was used. [Example]

[0088] Drometrizole trisiloxane was obtained in the same manner as in Example 1, except that 100 parts by weight of tripotassium phosphate was used. [Example]

[0089] Drometrizole trisiloxane was obtained in the same manner as in Example 1, except that 30 parts by weight of ethyl acetate and 170 parts by weight of methanol were used. [Example]

[0090] Drometrizole trisiloxane was obtained in the same manner as in Example 1, except that a fourth mixture was prepared by mixing 150 parts by weight of the methallyl drometrizole and 100 parts by weight of acetone at room temperature under a nitrogen atmosphere. [Example]

[0091] Drometrizole trisiloxane was obtained in the same manner as in Example 1, except that a fourth mixture was prepared by mixing 150 parts by weight of methallyl drometrizole, 80 parts by weight of methyl ethyl ketone, and 20 parts by weight of acetone at room temperature under a nitrogen atmosphere.

[0092] (Comparative Example 1) Drometrizole trisiloxane was obtained in the same manner as in Example 1, except that carbonate (K2CO3) was used instead of tripotassium phosphate.

[0093] The yields of DMTS prepared in the examples and comparative examples were measured and are shown in Table 1.

[0094] [Table 1]

[0095] From the results in Table 1, it can be seen that Examples 1 to 8 have high yields, and in particular Examples 1, 7 and 8 have the best yields.

[0096] On the other hand, it can be seen that Comparative Example 1 is inferior to the Examples in the above characteristics.

Claims

1. (a) combining drometrizole, a phosphate salt, and a solvent to form a first mixture; (b) adding methallyl halide to the first mixture and reacting to prepare a first product; (c) adding distilled water to the first product followed by phase separation to form a second mixture; (d) distilling the second mixture to remove the solvent and then heating to prepare methallyl drometrizole; (e) mixing the methallyl drometrizole with a solvent to form a third mixture; (f) cooling, crystallizing, filtering, and drying the third mixture to obtain methallyl drometrizole; (g) mixing the methallyl drometrizole with a solvent to form a fourth mixture; (h) mixing the fourth mixture with a catalyst solution to form a fifth mixture; (i) mixing and reacting the fifth mixture with a heptamethyltrisiloxane (HMTS) solution to prepare a second product; (j) distilling the second product to remove solvent and then adding a solvent to form a sixth mixture; (k) cooling, crystallizing, filtering, and drying the sixth mixture to obtain drometrizole trisiloxane (DMTS).

2. 2. The method for preparing DMTS according to claim 1, wherein the phosphate salt in step (a) is tripotassium phosphate.

3. 3. The method for preparing DMTS according to claim 2, wherein step (a) uses a mixture of ethyl acetate and dimethyl sulfoxide as a solvent.

4. 4. The method for preparing DMTS according to claim 3, wherein step (d) comprises distilling the second mixture to remove the solvent, and then reacting the second mixture at 190 to 250°C for 30 minutes to 5 hours to prepare methallyl drometrizole.

5. 5. The method for preparing DMTS according to claim 4, wherein step (e) uses a mixture of ethyl acetate and methanol as a solvent.

6. 6. The method for preparing DMTS according to claim 5, wherein step (g) uses methyl ethyl ketone or acetone as a solvent.

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